Develop new chemotherapy for a series of related parsitic diseases, namely leishmaniasis, Chagas disease and malaria. Millions of people worldwide are influenced by these diseases. Current therapy for them is unsatisfactory due to the emergence of drug resistance. With the aid of molecular modeling and combinatorial chemistry, libraries of nonpeptide inhibitors of L. major cpB based on a previous lead PS28, a library of hydroxyethylamine isostere inhibitors of cruzain, a library of urea inhibitors of falcipain will be designed and synthesized. As these enzymes are homologous, each library of inhibitors will be assayed for all three enzymes, for their ability to inhibit parasite growth as well as their toxicity.